Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation
文献类型：期刊论文
| 作者 | Su LY1,2; Li H1,2; Lv L1,2; Feng YM1; Li GD1,2,4; Luo RC1; Zhou HJ1; Lei XG1; Ma L1,2; Li JL1,3 |
| 刊名 | AUTOPHAGY
 |
| 出版日期 | 2015 |
| 卷号 | 11期号:10页码:1745-1759 |
| 关键词 | Autophagy CDK5 MPTP SNCA TH melatonin |
| 通讯作者 | xthu@mail.kiz.ac.cn ; yaoyg@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | Autophagy is involved in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). However, little is known about the regulation of autophagy in neurodegenerative process. In this study, we characterized aberrant activation of autophagy induced by neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and demonstrated that melatonin has a protective effect on neurotoxicity. We found an excessive activation of autophagy in monkey brain tissues and C6 cells, induced by MPTP, which is mediated by CDK5 (cyclin-dependent kinase 5). MPTP treatment significantly reduced total dendritic length and dendritic complexity of cultured primary cortical neurons and melatonin could reverse this effect. Decreased TH (tyrosine hydroxylase)-positive cells and dendrites of dopaminergic neurons in the substantia nigra pars compacta (SNc) were observed in MPTP-treated monkeys and mice. Along with decreased TH protein level, we observed an upregulation of CDK5 and enhanced autophagic activity in the striatum of mice with MPTP injection. These changes could be salvaged by melatonin treatment or knockdown of CDK5. Importantly, melatonin or knockdown of CDK5 reduced MPTP-induced SNCA/α-synuclein aggregation in mice, which is widely thought to trigger the pathogenesis of PD. Finally, melatonin or knockdown of CDK5 counteracted the PD phenotype in mice induced by MPTP. Our findings uncover a potent role of CDK5-mediated autophagy in the pathogenesis of PD, and suggest that control of autophagic pathways may provide an important clue for exploring potential target for novel therapeutics of PD. |
| 收录类别 | 其他 |
| 资助信息 | This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003, XDB02020001), the National Natural Science Foundation of China (31171225), and the Ministry of Science and Technology of China (2011CB910900). |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/9359]  |
| 专题 | 昆明动物研究所_神经系统编码 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_学习记忆的分子神经机制 昆明动物研究所_重大疾病机理的遗传学 昆明动物研究所_表观遗传与神经退行性疾病 昆明动物研究所_中国科学院昆明灵长类研究中心 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences; Kunming Institute of Zoology; Kunming, Yunnan, China 2.Kunming College of Life Science; University of Chinese Academy of Sciences; Kunming, Yunnan, China 3.Kunming Primate Research Center of the Chinese Academy of Sciences; Kunming Institute of Zoology; Chinese Academy of Sciences; Kunming, Yunnan, China 4.School of Life Science; Anhui University; Hefei, Anhui, China 5.CAS Center for Excellence in Brain Science and Intelligence Technology; Chinese Academy of Sciences; Shanghai, China |
| 推荐引用方式 GB/T 7714 | Su LY,Li H,Lv L,et al. Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation[J]. AUTOPHAGY,2015,11(10):1745-1759. |
| APA | Su LY.,Li H.,Lv L.,Feng YM.,Li GD.,...&Yao YG[*].(2015).Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation.AUTOPHAGY,11(10),1745-1759. |
| MLA | Su LY,et al."Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation".AUTOPHAGY 11.10(2015):1745-1759. |
入库方式： OAI收割
来源：昆明动物研究所
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